PROJECT SUMMARY Valvular heart disease is a significant cause of global morbidity and mortality. Evolving treatment guidelines support earlier intervention and valve repair when possible. Advances in repair techniques have progressed in the clinical arena primarily based upon anatomic and physiologic premises and occasionally based upon visual and echocardiographic appearance. Yet, the biomechanical engineering fundamentals and principles underlying valvuloplasty operations are rarely investigated. A more robust understanding of such principles and incorporation into surgical procedures may enhance valve reparability and durability and thus ultimately translate into less thromboembolic and hemorrhagic sequelae of long term anticoagulation for mechanical valve replacement and less perioperative risks of reintervention for bioprosthetic valve deterioration. We have designed and produced a novel 3D-printed left heart simulator into which mitral and aortic valve specimens can be mounted and studied throughout the cardiac cycle. Multiple regurgitant disease states can be reproduced, as can the current clinically-employed repair operations. Innovative biomechanical sensors and imaging technologies facilitate the detailed analysis of the engineering principles within these operations. Comparisons of and identification of notable functional differences among contemporary operative techniques have already been discovered and published from investigations performed using this heart valve system. We propose to study in depth aortic and mitral valve repair operations ex vivo and then validate findings in large animal models. We are optimistic that the proposed experiments will yield important knowledge on current and potential future clinical therapies for valve disease and can be rapidly translated to intraoperative patient care.